Ophthalmology – Lyme Disease

Basics

Description

Lyme disease is a multisystem infectious disease caused by Borrelia burgdorferi, a spirochete transmitted by infected Ixodes ticks.

It may involve the:

• Skin
• Nervous system
• Heart
• Joints
• Eyes

Ocular involvement can occur at several stages and may affect almost any ocular structure.

Epidemiology

Lyme disease is one of the most common tick-borne diseases in temperate regions of the Northern Hemisphere.

It is especially important in endemic regions of:

• Northeastern United States
• Mid-Atlantic United States
• Upper Midwest
• Europe
• Parts of Asia

Cases occur most often during spring, summer, and early fall, corresponding to periods of tick activity.

Risk Factors

Important risk factors include:

• Residence in an endemic area
• Travel to an endemic area
• Outdoor exposure in wooded or grassy areas
• Tick bite
• Exposure to deer, rodents, and tick-infested environments

General Prevention

The most effective preventive strategy is avoidance of tick bites.

Measures include:

• Avoiding dense brush and tall grasses when possible
• Wearing long sleeves and long pants
• Wearing light-colored clothing to make ticks easier to identify
• Using appropriate tick repellents such as DEET
• Performing a thorough skin and scalp examination after outdoor activity
• Showering after returning indoors
• Checking children carefully for ticks
• Checking outdoor pets
• Removing attached ticks promptly

Etiology

Lyme disease is caused by Borrelia burgdorferi, a motile spirochete.

Transmission occurs through the bite of infected Ixodes ticks.

Small mammals, especially rodents, act as important reservoirs.

Humans are incidental hosts.

Person-to-person transmission does not occur through ordinary contact.

Pathophysiology

After entering through the skin, the organism can disseminate through tissues and the bloodstream.

Borrelia can evade host immunity through changes in its surface proteins and interaction with complement regulatory pathways.

The clinical manifestations result from:

• Direct infection
• Tissue invasion
• Host inflammatory response
• Immune-mediated injury

Ocular manifestations may therefore reflect either active infection or secondary immune inflammation.

Diagnosis

History

Important questions include:

• Recent tick bite
• Travel to or residence in an endemic area
• Outdoor exposure
• Previous erythema migrans rash
• Fever or flu-like symptoms
• Joint pain
• Cardiac symptoms
• Neurologic symptoms

Ocular symptoms may include:

• Blurred vision
• Eye pain
• Redness
• Diplopia
• Floaters
• Photophobia
• Progressive visual loss

Clinical Stages

Early Localized Disease

The classic early manifestation is erythema migrans.

This is usually:

• Expanding
• Erythematous
• Often greater than several centimeters
• Sometimes associated with central clearing

It may produce the classic bull’s-eye appearance, although many lesions do not have this exact morphology.

The rash is often neither painful nor itchy.

Associated symptoms may include:

• Fever
• Chills
• Fatigue
• Headache
• Myalgia
• Arthralgia
• Lymphadenopathy

Early Ocular Findings

Possible findings include:

• Conjunctivitis
• Periorbital edema

Early Disseminated Disease

Dissemination can occur over weeks to months.

Systemic manifestations may involve:

• Nervous system
• Heart
• Joints
• Skin

Neurologic Manifestations

These may include:

• Meningitis
• Cranial neuropathy
• Radiculopathy
• Facial nerve palsy
• Headache
• Photophobia

Cardiac Manifestations

These may include:

• Palpitations
• Arrhythmia
• Atrioventricular block

Ocular Manifestations

Lyme disease can produce a broad range of ophthalmic findings.

External and Anterior Segment

Possible manifestations include:

• Conjunctivitis
• Episcleritis
• Scleritis
• Keratitis
• Exposure keratopathy secondary to facial nerve palsy
• Anterior uveitis
• Granulomatous uveitis

Cranial Nerve Palsies

Lyme disease can involve cranial nerves, including:

• CN III
• CN IV
• CN VI
• CN VII

Patients may present with:

• Diplopia
• Ptosis
• Extraocular motility abnormalities
• Facial weakness

Facial nerve palsy may lead to lagophthalmos and exposure keratopathy.

Intermediate and Posterior Segment Disease

Reported manifestations include:

• Pars planitis
• Vitritis
• Choroiditis
• Retinitis
• Macular edema
• Retinal vascular occlusion
• Retinal vasculitis

These findings are less common than neurologic or anterior segment manifestations.

Optic Nerve Manifestations

Possible findings include:

• Optic neuritis
• Retrobulbar optic neuritis
• Optic disc edema
• Ischemic optic neuropathy
• Optic atrophy

Patients may develop:

• Reduced visual acuity
• Dyschromatopsia
• Relative afferent pupillary defect
• Visual field defects

Late Disease

Late manifestations can persist or recur over months to years.

Systemic disease may include:

• Arthritis
• Chronic neurologic manifestations
• Acrodermatitis chronica atrophicans in some geographic regions

Late ocular findings may include:

• Stromal keratitis
• Episcleritis
• Orbital myositis
• Chronic uveitis
• Rare severe visual pathway involvement

Physical Examination

A complete examination should include:

• General physical examination
• Neurologic examination
• Full ophthalmic examination

Ophthalmic assessment should include:

• Visual acuity
• Pupillary examination
• Ocular motility
• Cranial nerve testing
• Slit-lamp examination
• IOP
• Dilated fundus examination

Diagnostic Testing

Serology

Laboratory diagnosis is based on two-tier serologic testing in the appropriate clinical setting.

Modern testing generally begins with an antibody screening immunoassay followed by a confirmatory second assay according to current testing algorithms.

Interpretation depends heavily on:

• Timing of symptoms
• Clinical presentation
• Pretest probability

Early infection can be seronegative before antibodies develop.

Cerebrospinal Fluid

Lumbar puncture may be indicated when there is concern for:

• Meningitis
• Neuroborreliosis
• Significant neurologic manifestations

CSF evaluation may include:

• Cell count
• Protein
• Intrathecal antibody assessment when appropriate

Additional Testing

Depending on the differential diagnosis, testing may include:

• Syphilis serology
• Other infectious testing
• Neuroimaging
• OCT
• Fluorescein angiography

These are guided by the specific ocular manifestation.

Differential Diagnosis

For optic nerve edema, retinitis, or neuro-ophthalmic disease, important alternatives include:

• Syphilis
• Cat-scratch disease
• Toxoplasmosis
• Acute retinal necrosis
• Multiple sclerosis
• Other infectious or inflammatory uveitides

Treatment

Treatment depends on the stage of disease and whether neurologic involvement is present.

Early Lyme Disease

Oral antibiotics are typically used.

Common agents include:

• Doxycycline
• Amoxicillin
• Cefuroxime axetil

Selection depends on:

• Age
• Pregnancy status
• Allergies
• Clinical manifestation

Neuro-Ophthalmic or Neurologic Lyme Disease

Patients with meningitis, significant cranial neuropathy, or other neuroborreliosis may require more intensive antibiotic therapy.

Depending on the presentation, treatment may include:

• Oral doxycycline
• Intravenous ceftriaxone

The exact regimen should follow current infectious-disease guidelines.

Ocular Inflammation

Inflammatory ocular manifestations may require treatment in addition to antibiotics.

Examples include:

• Topical corticosteroids for anterior uveitis
• Cycloplegic agents for pain and synechiae prevention
• Systemic anti-inflammatory therapy in selected severe disease

Antimicrobial treatment of the underlying Lyme infection should not be omitted when active infection is suspected.

Tick Removal

An attached tick should be removed promptly with fine-tipped forceps.

Recommended technique:

• Grasp the tick close to the skin
• Pull upward steadily
• Avoid twisting
• Avoid crushing or squeezing the body
• Clean the bite site afterward

Prompt removal reduces the likelihood of transmission.

Follow-Up

Follow-up depends on the severity of ocular disease.

Patients with active uveitis, optic nerve disease, or significant neuro-ophthalmic manifestations require close monitoring.

Follow-up should assess:

• Visual acuity
• Pupillary function
• Ocular motility
• Degree of inflammation
• IOP
• Optic nerve appearance
• Retinal findings

Patient Education

Patients should be advised to:

• Use protective clothing outdoors
• Use tick repellent appropriately
• Perform skin checks
• Remove ticks promptly
• Seek evaluation for expanding rash or new neurologic symptoms
• Report new visual symptoms promptly

Prognosis

Most appropriately diagnosed and treated patients have a favorable outcome.

Prognosis depends on:

• Speed of diagnosis
• Severity of neurologic involvement
• Type of ocular involvement
• Presence of optic nerve or retinal damage

Some inflammatory manifestations may persist despite eradication of infection.

Complications

Ophthalmic complications can include:

• Chronic uveitis
• Keratitis
• Scleritis
• Cranial nerve palsy
• Optic neuropathy
• Retinal vasculitis
• Macular edema
• Permanent visual loss

Key Clinical Pearls

• Lyme disease is caused by Borrelia burgdorferi and transmitted by Ixodes ticks.
• The classic early manifestation is erythema migrans, but not every patient recalls a rash or tick bite.
• Ocular involvement is diverse and may include conjunctivitis, uveitis, cranial nerve palsies, keratitis, optic neuritis, and retinitis.
• Facial nerve palsy can produce lagophthalmos and exposure keratopathy.
• Diagnosis relies on clinical context plus appropriate serologic testing.
• In neuro-ophthalmic disease, consider neuroborreliosis and coordinate treatment with infectious disease or neurology.
• Always consider alternative diagnoses such as syphilis, cat-scratch disease, toxoplasmosis, and acute retinal necrosis when posterior segment or optic nerve findings are present.